This project aims to elucidate the biological function(s) of the human c-fps/fes proto-oncogene and to understand the molecular basis of its oncogenic potential. The coding sequence of human c- fps/fes was cloned into an efficient retroviral vector that allows the expression of very high levels of the c-fps/fes product NCP92. Using this DNA or rescued infectious virus, we demonstrated for the first time that when normal NCP92 was expressed at sufficiently high levels, it caused cell transformation in NIH 3T3 cells. By cloning c-fps/fes into different retroviral vectors, we showed that transforming activity was a direct function of the levels of expression of NCP92. The transforming activity of NCP92 could be manipulated at a second level, by modulating its tyrosine kinase activity in vivo. This was done by treatment of infected cells with sodium vanadate, a known inhibitor of tyrosine phosphatases. Vanadate treatment increased the transforming activity of NCP92 by 100-fold. The potentiating effect of vanadate was reversible, dose-dependent, and specific for the c-fps/fes proto-oncogene.